The role of ultraviolet light (UVL) and sunlight in the etiology of certain types of skin cancer seems well established. The mechanism(s) associated with these processes are not understood. It has been suggested that the carcinogenic activity of light is dependent upon the photochemical conversion of sterols to carcinogenic substances. The formation of a sterol-derived photoproduct with carcinogenic properties has now been demonstrated in UV-irradiated human and hairless mouse skin. The role of this compound, cholesterol alpha-oxide, in the etiology of UV-carcinogenesis is under investigation. This proposal is designed to determine whether additional information will implicate the compound in the etiology of UVL-carcinogenesis and involves: 1) Studies on the role of antioxidants in suppression of UVL-carcinogenesis; 2) Studies on the metabolism and detoxification of the carcinogen; 3) the ability of the carcinogenic compound to transform normal cells, in cell culture, to cells with malignant potential and; 4) the ability of the carcinogen to induce tumors when applied, in vivo, to mice. Should the carcinogen induce transformation in cell culture and initiate tumors in vivo, then an overwhelming body of evidence implicating the compound in the etiology of skin cancer will have been amassed. Studies of the metabolism of this compound may indicate means by which it's formation can be prevented. BIBLIOGRAPHIC REFERENCES: Chan, J. T. and H. S. Black (1976) Distribution of cholesterol-5 alpha, 6 alpha-Epoxide Formation and its Metabolism in Mouse Skin. J. Invest. Dermatol. 66, 112-116. Black, H. S. and J. L. Laseter (1976) The Isolation and Identification of Cholesterol-5 alpha, 6 alpha-Epoxide from Liver of Hairless Mice. Comp. Biochem. Physiol. 53C, 29-31.